Mirtazapine

Concomitant administration of diazepam (15 mg) had a minimal effect on plasma levels of mirtazapine (15 mg) in 12 healthy subjects. However, the impairment of motor skills produced by mirtazapine has been shown to be additive with those caused by diazepam. Accordingly, patients should be advised to avoid diazepam and other similar drugs while taking mirtazapine.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies were conducted with mirtazapine given in the diet at doses of 2, 20, and 200 mg/kg/day to mice and 2, 20, and 60 mg/kg/day to rats. The highest doses used are approximately 20 and 12 times the maximum recommended human dose (MRHD) of 45 mg/day on an mg/m² basis in mice and rats, respectively. There was an increased incidence of hepatocellular adenoma and carcinoma in male mice at the high dose. In rats, there was an increase in hepatocellular adenoma in females at the mid and high doses and in hepatocellular tumors and thyroid follicular adenoma/cystadenoma and carcinoma in males at the high dose. The data suggest that the above effects could possibly be mediated by non-genotoxic mechanisms, the relevance of which to humans is not known. 

The doses used in the mouse study may not have been high enough to fully characterize the carcinogenic potential of mirtazapine tablets.

Mutagenesis

Mirtazapine was not mutagenic or clastogenic and did not induce general DNA damage as determined in several genotoxicity tests: Ames test, in vitro gene mutation assay in Chinese hamster V 79 cells, in vitro sister chromatid exchange assay in cultured rabbit lymphocytes, in vivo bone marrow micronucleus test in rats, and unscheduled DNA synthesis assay in HeLa cells.

Impairment of Fertility

In a fertility study in rats, mirtazapine was given at doses up to 100 mg/kg [ 20 times the maximum recommended human dose  (MRHD) on a mg/m² basis] . Mating and conception were not affected by the drug, but estrous cycling was disrupted at doses that were 3 or more times the MRHD, and pre-implantation losses occurred at 20 times the MRHD.

Pregnancy

Teratogenic Effects – Pregnancy Category C

Reproduction studies in pregnant rats and rabbits at doses up to 100 mg/kg and 40 mg/kg, respectively [ 20 and 17 times the maximum recommended human dose (MRHD) on an mg/m² basis, respectively] , have revealed no evidence of teratogenic effects. However, in rats, there was an increase in postimplantation losses in dams treated with mirtazapine. There was an increase in pup deaths during the first 3 days of lactation and a decrease in pup birth weights. The cause of these deaths is not known. The effects occurred at doses that were 20 times the MRHD, but not at 3 times the MRHD, on an mg/m² basis. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Because some mirtazapine may be excreted into breast milk, caution should be exercised when mirtazapine tablets are administered to nursing women.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established (see BOXED WARNINGand WARNINGS: Clinical Worsening and Suicide Risk). Two placebo-controlled trials in 258 pediatric patients with MDD have been conducted with mirtazapine tablets, and the data were not sufficient to support a claim for use in pediatric patients. Anyone considering the use of mirtazapine tablets in a child or adolescent must balance the potential risks with the clinical need. 

In an 8-week-long pediatric clinical trial of doses between 15 to 45 mg/day, 49% of mirtazapine-treated patients had a weight gain of at least 7%, compared to 5.7% of placebo-treated patients.  The mean increase in weight was 4 kg (2 kg SD) for mirtazapine-treated patients versus 1 kg (2 kg SD) for placebo-treated patients (see PRECAUTIONS: Increased Appetite/Weight Gain).

Geriatric Use

Approximately 190 elderly individuals (≥ 65 years of age) participated in clinical studies with mirtazapine tablets. This drug is known to be substantially excreted by the kidney (75%), and the risk of decreased clearance of this drug is greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection. Sedating drugs may cause confusion and over-sedation in the elderly. No unusual adverse age-related phenomena were identified in this group. Pharmacokinetic studies revealed a decreased clearance in the elderly. Caution is indicated in administering mirtazapine to elderly patients (see CLINICAL PHARMACOLOGYand DOSAGE AND ADMINISTRATION).

MIRTAZAPINE ADVERSE REACTIONS

Associated with Discontinuation of Treatment

Approximately 16 % of the 453 patients who received mirtazapine tablets in US 6-week controlled clinical trials discontinued treatment due to an adverse experience, compared to 7 % of the 361 placebo-treated patients in those studies. The most common events (≥ 1%) associated with discontinuation and considered to be drug related (i.e., those events associated with dropout at a rate at least twice that of placebo) included in Table 2.

Table 2: Common Adverse Events Associated With Discontinuation of Treatment in 6-Week U.S.
Mirtazapine Trials

Commonly Observed Adverse Events in U.S. Controlled Clinical Trials

The most commonly observed adverse events associated with the use of mirtazapine tablets (incidence of 5% or greater) and not observed at an equivalent incidence among placebo-treated patients (mirtazapine incidence at least twice that for placebo) are listed in Table 3.


Table 3: Common Treatment –Emergent Adverse Events Associated With the Use of Mirtazapine
in 6-Week U.S. Trials

Adverse Events Occurring at an Incidence of 1% or More Among Mirtazapine-Treated Patients

Table 4 enumerates adverse events that occurred at an incidence of 1% or more, and were more frequent than in the placebo group, among mirtazapine tablets-treated patients who participated in short-term US placebo-controlled trials in which patients were dosed in a range of 5 to 60 mg/day. This table shows the percentage of patients in each group who had at least 1 episode of an event at some time during their treatment. Reported adverse events were classified using a standard COSTART-based dictionary terminology.

The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side-effect incidence rate in the population studied.

Table 4: Incidence of Adverse Clinical Experiences¹ (≥1%) in Short-Term U.S. Controlled Studies

ECG Changes

The electrocardiograms for 338 patients who received mirtazapine tablets and 261 patients who received placebo in 6-week, placebo-controlled trials were analyzed. Prolongation in QTc ≥ 500 msec was not observed among mirtazapine-treated patients; mean change in QTc was +1.6 msec for mirtazapine and –3.1 msec for placebo. Mirtazapine was associated with a mean increase in heart rate of 3.4 bpm, compared to 0.8 bpm for placebo. The clinical significance of these changes is unknown.

Other Adverse Events Observed During the Premarketing Evaluation of Mirtazapine

During its premarketing assessment, multiple doses of mirtazapine tablets were administered to 2796 patients in clinical studies. The conditions and duration of exposure to mirtazapine varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, fixed-dose and titration studies. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories.

In the tabulations that follow, reported adverse events were classified using a standard COSTART-based dictionary terminology. The frequencies presented, therefore, represent the proportion of the 2796 patients exposed to multiple doses of mirtazapine who experienced an event of the type cited on at least 1 occasion while receiving mirtazapine. All reported events are included except those already listed in Table 4, those adverse experiences subsumed under COSTART terms that are either overly general or excessively specific so as to be uninformative, and those events for which a drug cause was very remote.

It is important to emphasize that, although the events reported occurred during treatment with mirtazapine, they were not necessarily caused by it.

Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Only those events not already listed in Table 4 appear in this listing. Events of major clinical importance are also described in the WARNINGS and PRECAUTIONS sections.

Body as a Whole: frequent: malaise, abdominal pain, abdominal syndrome acute; infrequent: chills, fever, face edema, ulcer, photosensitivity reaction, neck rigidity, neck pain, abdomen enlarged; rare: cellulitis, chest pain substernal.

Cardiovascular System: frequent: hypertension, vasodilatation; infrequent: angina pectoris, myocardial infarction, bradycardia, ventricular extrasystoles, syncope, migraine, hypotension; rare: atrial arrhythmia, bigeminy, vascular headache, pulmonary embolus, cerebral ischemia, cardiomegaly, phlebitis, left heart failure.

Digestive System: frequent: vomiting, anorexia; infrequent: eructation, glossitis, cholecystitis, nausea and vomiting, gum hemorrhage, stomatitis, colitis, liver function tests abnormal; rare:  tongue discoloration, ulcerative stomatitis, salivary gland enlargement, increased salivation, intestinal obstruction, pancreatitis, aphthous stomatitis, cirrhosis of liver, gastritis, gastroenteritis, oral moniliasis, tongue edema.

Endocrine System: rare: goiter, hypothyroidism.

Hemic and Lymphatic System: rare: lymphadenopathy, leukopenia, petechia, anemia, thrombocytopenia, lymphocytosis, pancytopenia.

Metabolic and Nutritional Disorders: frequent: thirst; infrequent: dehydration, weight loss; rare: gout, SGOT increased, healing abnormal, acid phosphatase increased, SGPT increased, diabetes mellitus, hyponatremia.

Musculoskeletal System:   frequent: myasthenia, arthralgia; infrequent:  arthritis, tenosynovitis; rare: pathologic fracture, osteoporosis fracture, bone pain, myositis, tendon rupture, arthrosis, bursitis.

Nervous System: frequent: hypesthesia, apathy, depression, hypokinesia, vertigo, twitching, agitation, anxiety, amnesia, hyperkinesia , paresthesia; infrequent: ataxia, delirium, delusions, depersonalization, dyskinesia, extrapyramidal syndrome, libido increased, coordination abnormal, dysarthria, hallucinations, manic reaction, neurosis, dystonia, hostility, reflexes increased, emotional lability, euphoria, paranoid reaction; rare:  aphasia, nystagmus, akathisia (psychomotor restlessness), stupor, dementia, diplopia, drug dependence, paralysis, grand mal convulsion, hypotonia, myoclonus, psychotic depression, withdrawal syndrome, serotonin syndrome.

Respiratory System:  frequent:  cough increased, sinusitis; infrequent:  epistaxis, bronchitis, asthma, pneumonia; rare: asphyxia, laryngitis, pneumothorax, hiccup.

Skin and Appendages: frequent:  pruritus, rash; infrequent:  acne, exfoliative dermatitis, dry skin, herpes simplex, alopecia; rare: urticaria, herpes zoster, skin hypertrophy, seborrhea, skin ulcer.

Special Senses: infrequent: eye pain, abnormality of accommodation, conjunctivitis, deafness, keratoconjunctivitis, lacrimation disorder, glaucoma, hyperacusis, ear pain; rare: blepharitis, partial transitory deafness, otitis media, taste loss, parosmia.

Urogenital System: frequent: urinary tract infection; infrequent: kidney calculus, cystitis, dysuria, urinary incontinence, urinary retention, vaginitis, hematuria, breast pain, amenorrhea, dysmenorrhea, leukorrhea, impotence; rare: polyuria, urethritis, metrorrhagia, menorrhagia, abnormal ejaculation, breast engorgement, breast enlargement, urinary urgency.

Other Adverse Events Observed During Postmarketing Evaluation of Mirtazapine

Adverse events reported since market introduction, which were temporally (but not necessarily casually) related to mirtazapine therapy, include 4 cases of the ventricular arrhythmia torsades de pointes. In 3 of the 4 cases, however, concomitant drugs were implicated. All patients recovered.

Cases of severe skin reactions, including Stevens-Johnson syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis have also been reported.

DRUG ABUSE AND DEPENDENCE

Controlled Substance Class

Mirtazapine tablets are not a controlled substance.

Physical and Psychological Dependence

Mirtazapine tablets have not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. While the clinical trials did not reveal any tendency for any drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted and/or abused once marketed. Consequently, patients should be evaluated carefully for history of drug abuse, and such patients should be observed closely for signs of mirtazapine misuse or abuse (e.g., development of tolerance, incrementations of dose, drug-seeking behavior).

OVERDOSAGE

Human Experience

There is very limited experience with mirtazapine tablets overdose. In premarketing clinical studies, there were 8 reports of mirtazapine overdose alone or in combination with other pharmacological agents. The only drug overdose death reported while taking mirtazapine was in combination with amitriptyline and chlorprothixene in a non-US clinical study. Based on plasma levels, the mirtazapine dose taken was 30 to 45 mg, while plasma levels of amitriptyline and chlorprothixene were found to be at toxic levels. All other premarketing overdose cases resulted in full recovery. Signs and symptoms reported in association with overdose included disorientation, drowsiness, impaired memory, and tachycardia. There were no reports of ECG abnormalities, coma or convulsions following overdose with mirtazapine tablets alone.

Overdose Management

Treatment should consist of those general measures employed in the management of overdose with any drug effective in the treatment of major depressive disorder. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. There is no experience with the use of forced diuresis, dialysis, hemoperfusion, or exchange transfusion in the treatment of mirtazapine overdosage. No specific antidotes for mirtazapine are known.
 
In managing overdosage, consider the possibility of multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the Physicians’ Desk Reference (PDR).

MIRTAZAPINE DOSAGE AND ADMINISTRATION

Initial Treatment

The recommended starting dose for mirtazapine tablets is 15 mg/day, administered in a single dose, preferably in the evening prior to sleep. In the controlled clinical trials establishing the efficacy of mirtazapine in the treatment of major depressive disorder, the effective dose range was generally 15 to 45 mg/day. While the relationship between dose and satisfactory response in the treatment of major depressive disorder for mirtazapine has not been adequately explored, patients not responding to the initial 15 mg dose may benefit from dose increases up to a maximum of 45 mg/day. Mirtazapine has an elimination half-life of approximately 20 to 40 hours; therefore, dose changes should not be made at intervals of less than 1 to 2 weeks in order to allow sufficient time for evaluation of the therapeutic response to a given dose.

Elderly and Patients with Renal or Hepatic Impairment

The clearance of mirtazapine is reduced in elderly patients and in patients with moderate to severe renal or hepatic impairment. Consequently, the prescriber should be aware that plasma mirtazapine levels may be increased in these patient groups, compared to levels observed in younger adults without renal or hepatic impairment (see PRECAUTIONS and CLINICAL PHARMACOLOGY).

Maintenance/Extended Treatment

It is generally agreed that acute episodes of depression require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of mirtazapine tablets has demonstrated that its efficacy in major depressive disorder is maintained for periods of up to 40 weeks following 8 to 12 weeks of initial treatment at a dose of 15 to 45 mg/day (see CLINICAL PHARMACOLOGY). Based on these limited data, it is unknown whether or not the dose of mirtazapine needed for maintenance treatment is identical to the dose needed to achieve an initial response. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment.

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with mirtazapine tablets. Conversely, at least 14 days should be allowed after stopping mirtazapine tablets before starting an MAOI intended to treat psychiatric disorders (see CONTRAINDICATIONS).

Use of Mirtazapine Tablets With Other MAOIs, Such as Linezolid or Methylene Blue

Do not start mirtazapine tablets in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered (see CONTRAINDICATIONS).

In some cases, a patient already receiving therapy with mirtazapine tabletsmay require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue treatment are judged to outweigh the risks of serotonin syndrome in a particular patient, mirtazapine tabletsshould be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with mirtazapine tabletsmay be resumed 24 hours after the last dose of linezolid or intravenous methylene blue (see WARNINGS).

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with mirtazapine tabletsis unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use (see WARNINGS).

Discontinuation of Mirtazapine Tablets Treatment

Symptoms associated with the discontinuation or dose reduction of mirtazapine tablets have been reported. Patients should be monitored for these and other symptoms when discontinuing treatment or during dosage reduction. A gradual reduction in the dose over several weeks, rather than abrupt cessation, is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, dose titration should be managed on the basis of the patient’s clinical response (see PRECAUTIONS and ADVERSE REACTIONS).

HOW SUPPLIED

Mirtazapine tablets, USP are supplied as:

7.5 mg Tablets – White, biconvex, capsule shaped film coated tablets with “11” debossed on one side and “A” debossed on the other side.

Bottles of 30                                                    NDC 13107-001-30
Bottles of 60                                                    NDC 13107-001-60
Bottles of 90                                                    NDC 13107-001-90
Bottles of 100                                                  NDC 13107-001-01
Bottles of 500                                                  NDC 13107-001-05

15 mg Tablets – Yellow, biconvex, capsule shaped film coated tablets with a score line in between “0” and “8” on one side and “A” debossed on the other side.

Bottles of 30 (120 cc container)                        NDC 13107-031-30
Bottles of 30(30 cc container)                           NDC 13107-031-34
Bottles of 60                                                    NDC 13107-031-60
Bottles of 90                                                    NDC 13107-031-90
Bottles of 100                                                  NDC 13107-031-01
Bottles of 500                                                  NDC 13107-031-05
30 Unit-of-use packaging                                 NDC 13107-031-32

30 mg Tablets – Reddish Brown, biconvex, capsule shaped film coated tablets with a score line in between “0” and “9” on one side and “A” debossed on the other side.

Bottles of 30 (120 cc container)                        NDC 13107-003-30
Bottles of 30(30 cc container)                           NDC 13107-003-34
Bottles of 60                                                    NDC 13107-003-60
Bottles of 90                                                    NDC 13107-003-90
Bottles of 100                                                  NDC 13107-003-01
Bottles of 500                                                  NDC 13107-003-05
30 Unit-of-use packaging                                 NDC 13107-003-32
 
45 mg Tablets – White, biconvex, capsule shaped film coated tablets with “10” debossed on one side and “A” debossed on the other side.

Bottles of 30(30 cc container)                           NDC 13107-032-34
Bottles of 60                                                    NDC 13107-032-60
Bottles of 90                                                    NDC 13107-032-90
Bottles of 100                                                  NDC 13107-032-01
Bottles of 500                                                  NDC 13107-032-05
30 Unit-of-use packaging                                 NDC 13107-032-32

Storage

Store at 25° C (77° F); excursions permitted to 15° to 30° C (59° to 86° F) [ see USP Controlled Room Temperature] . Protect from light and moisture.

Manufactured by:
Aurolife Pharma LLC
Dayton, NJ 08810
 
Manufactured for:
Aurobindo Pharma USA, Inc.
Dayton, NJ 08810
 
Revised: 01/2013

Medication Guide

Mirtazapine Tablets, USP


Read the Medication Guide that comes with mirtazapine tablets before you start taking them and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about mirtazapine tablets, talk to your healthcare provider.

What is the most important information I should know about mirtazapine tablets?

Mirtazapine tablets and other antidepressant medicines may cause serious side effects, including:

1. Suicidal thoughts or actions:

• Mirtazapine tablets and other antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, or young adults within the first few months of treatment or when the dose is changed.
• Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions.
• Watch for these changes and call your healthcare provider right away if you notice:
  • 
    New or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe.
  • 
    Pay particular attention to such changes when mirtazapine tablets are started or when the dose is changed.

Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms.

Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you:

• attempts to commit suicide
• acting on dangerous impulses
• acting aggressive or violent
• thoughts about suicide or dying
• new or worse depression 
• new or worse anxiety or panic attacks 
• feeling agitated, restless, angry or irritable 
• trouble sleeping
• an increase in activity or talking more than what is normal for you
• other unusual changes in behavior or mood

Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency. Mirtazapine tablets may be associated with these serious side effects:

2. Manic episodes:

• greatly increased energy
• severe trouble sleeping
• racing thoughts
• reckless behavior
• unusually grand ideas
• excessive happiness or irritability 
• talking more or faster than usual

3. Decreased White Blood Cellscalled neutrophils, which are needed to fight infections. Tell your doctor if you have any indication of infection such as fever, chills, sore throat, or mouth or nose sores, especially symptoms which are flu-like.

4. Serotonin Syndrome. This condition can be life-threatening and may include:

• agitation, hallucinations, coma or other changes in mental status
• coordination problems or muscle twitching (overactive reflexes)
• racing heartbeat, high or low blood pressure
• sweating or fever
• nausea, vomiting, or diarrhea
• muscle rigidity

5. Seizures

6. Low salt (sodium) levels in the blood. Elderly people may be at greater risk for this. Symptoms may include:

• headache
• weakness or feeling unsteady
• confusion, problems concentrating or thinking or memory problems

7. Sleepiness. It is best to take mirtazapine tablets close to bedtime.

8. Severe skin reactions: Call your doctor right away if you have any or all of the following symptoms:

• severe rash with skin swelling (including on the palms of the hands and soles of the feet)
• painful reddening of the skin and/or blisters/ulcers on the body or in the mouth

9. Severe allergic reactions: trouble breathing, swelling of the face, tongue, eyes or mouth

• rash, itchy welts (hives) or blisters, alone or with fever or joint pain

10. Increases in appetite or weight. Children and adolescents should have height and weight monitored during treatment.

11. Increased cholesterol and triglyceride levels in your blood

Do not stop mirtazapine tablets without first talking to your healthcare provider . Stopping mirtazapine tablets too quickly may cause potentially serious symptoms including:

• dizziness
• abnormal dreams
• agitation 
• anxiety
• fatigue
• confusion 
• headache
• shaking
• tingling sensation
• nausea, vomiting
• sweating

What are mirtazapine tablets?

Mirtazapine tablets are a prescription medicine used to treat depression. It is important to talk with your healthcare provider about the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider.

Talk to your healthcare provider if you do not think that your condition is getting better with mirtazapine tablets treatment.

Who should not take mirtazapine tablets?

Do not take mirtazapine tablets:

• if you are allergic to mirtazapine or any of the ingredients in mirtazapine tablets. See the end of this Medication Guide for a complete list of ingredients in mirtazapine tablets.
• if you take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid.
• Do not take an MAOI within 2 weeks of stopping mirtazapine tablets unless directed to do so by your physician.
• Do not start mirtazapine tablets if you stopped taking an MAOI in the last 2 weeks unless directed to do so by your physician.

People who take mirtazapine tablets close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms:

• high fever
• uncontrolled muscle spasms
• stiff muscles
• rapid changes in heart rate or blood pressure 
• confusion
• loss of consciousness (pass out)

What should I tell my healthcare provider before taking mirtazapine tablets? Ask if you are not sure.

Before starting mirtazapine tablets, tell your healthcare provider if you:

• Are taking certain drugs such as:
  • Triptans used to treat migraine headache
  • Medicines used to treat mood, anxiety, psychotic or thought disorders, including tricyclics, lithium, SSRIs, SNRIs, or antipsychotics
  • Tramadol used to treat pain
  • Over-the-counter supplements such as tryptophan or St. John's Wort
  • Phenytoin, carbamazepine, or rifampicin (these drugs can decrease your blood level of mirtazapine)
  • Cimetidine or ketoconazole (these drugs can increase your blood level of mirtazapine)
• Have or had:
  • liver problems
  • kidney problems
  • heart problems
  • seizures or convulsions
  • bipolar disorder or mania 
  • a tendency to get dizzy or faint
• are pregnant or plan to become pregnant. It is not known if mirtazapine tablets will harm your unborn baby. Talk to your healthcare provider about the benefits and risks of treating depression during pregnancy
• are breastfeeding or plan to breastfeed. Some mirtazapine may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking mirtazapine tablets

Tell your healthcare provider about all the medicines that you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Mirtazapine tablets and some medicines may interact with each other, may not work as well, or may cause serious side effects.

Your healthcare provider or pharmacist can tell you if it is safe to take mirtazapine tablets with your other medicines. Do not start or stop any medicine while taking mirtazapine tablets without talking to your healthcare provider first.

If you take mirtazapine tablets, you should not take any other medicines that contain mirtazapine including mirtazapine orally disintegrating tablets.

How should I take mirtazapine tablets?

• Take mirtazapine tablets exactly as prescribed. Your healthcare provider may need to change the dose of mirtazapine tablets until it is the right dose for you.
• Take mirtazapine tablets at the same time each day, preferably in the evening at bedtime.
• Swallow mirtazapine tablets as directed.
• It is common for antidepressant medicines such as mirtazapine tablets to take up to a few weeks before you start to feel better. Do not stop taking mirtazapine tablets if you do not feel results right away. 
• Do not stop taking or change the dose of mirtazapine tablets without first talking to your doctor, even if you feel better.
• Mirtazapine tablets may be taken with or without food.
• If you miss a dose of mirtazapine tablets, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of mirtazapine tablets at the same time.
• If you take too much mirtazapine, call your healthcare provider or poison control center right away, or get emergency treatment.

What should I avoid while taking mirtazapine tablets?

• Mirtazapine tablets can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how mirtazapine tablets affect you.
• Avoid drinking alcohol or taking diazepam (a medicine used for anxiety, insomnia and seizures, for example) or similar medicines while taking mirtazapine tablets. If you are uncertain about whether certain medication can be taken with mirtazapine tablets, please discuss with your doctor.

What are the possible side effects of mirtazapine tablets?

Mirtazapine tablets may cause serious side effects, including all of those described in the section entitled "What is the most important information I should know about mirtazapine tablets?"

Common possible side effects in people who take mirtazapine tablets include:

• sleepiness
• increased appetite, weight gain
• dry mouth
• constipation 
• dizziness
• abnormal dreams

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of mirtazapine tablets. For more information, ask your healthcare provider or pharmacist.

CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO THE FDA AT 1-800-FDA-1088.

How should I store mirtazapine tablets?

• Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
• Protect from light and moisture.

Keep mirtazapine tablets and all medicines out of the reach of children.

General information about mirtazapine tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use mirtazapine tablets for a condition for which it was not prescribed. Do not give mirtazapine tablets to other people, even if they have the same condition. They may harm them.

This Medication Guide summarizes the most important information about mirtazapine tablets. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about mirtazapine tablets that is written for healthcare professionals.

For more information about mirtazapine tablets, call 1-866-850-2876.

What are the ingredients in mirtazapine tablets?

Active ingredient: mirtazapine

Inactive ingredients: corn starch, hydroxypropyl cellulose, magnesium stearate, colloidal silicon dioxide, lactose monohydrate, hypromellose, and titanium dioxide. In addition, the 15 mg contains iron oxide yellow and 30 mg contains iron oxide red, iron oxide black, and iron oxide yellow.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Aurolife Pharma LLC

Dayton, NJ 08810

Manufactured for:

Aurobindo Pharma USA, Inc.

Dayton, NJ 08810

Revised: 01/2013

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL-7.5 mg 500 Tablets Bottle

NDC 13107-001-05
Mirtazapine Tablets, USP
7.5 mg
PHARMACIST:     PLEASE    DISPENSE    WITH
MEDICATION GUIDE PROVIDED SEPARATELY
Rx only           500 Tablets
AUROBINDO

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL-15 mg 500 Tablets Bottle

NDC 13107-031-05
Mirtazapine Tablets, USP
15 mg
PHARMACIST:     PLEASE    DISPENSE    WITH
MEDICATION GUIDE PROVIDED SEPARATELY
Rx only           500 Tablets
AUROBINDO

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL-30 mg 500 Tablets Bottle

NDC 13107-003-05
Mirtazapine Tablets, USP
30 mg
PHARMACIST:     PLEASE    DISPENSE    WITH
MEDICATION GUIDE PROVIDED SEPARATELY
Rx only           500 Tablets
AUROBINDO

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL-45 mg 500 Tablets Bottle

NDC 13107-032-05
Mirtazapine Tablets, USP
45 mg
PHARMACIST:     PLEASE    DISPENSE    WITH
MEDICATION GUIDE PROVIDED SEPARATELY
Rx only           500 Tablets
AUROBINDO

Mirtazapine Mirtazapine TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:13107-001 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength MIRTAZAPINE Mirtazapine 7.5 mg Inactive Ingredients Ingredient Name Strength STARCH, CORN hydroxypropyl cellulose MAGNESIUM STEARATE SILICON DIOXIDE lactose monohydrate HYDROXYPROPYL CELLULOSE, LOW SUBSTITUTED HYPROMELLOSE 2910 (6 MPA.S) titanium dioxide Product Characteristics Color Size Imprint Code Shape WHITE (White) 7 mm 11;A CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:13107-001-30 30 in 1 BOTTLE 2 NDC:13107-001-60 60 in 1 BOTTLE 3 NDC:13107-001-90 90 in 1 BOTTLE 4 NDC:13107-001-01 100 in 1 BOTTLE 5 NDC:13107-001-05 500 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA076921 2009-08-17

Mirtazapine Mirtazapine TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:13107-031 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength MIRTAZAPINE Mirtazapine 15 mg Inactive Ingredients Ingredient Name Strength STARCH, CORN hydroxypropyl cellulose MAGNESIUM STEARATE SILICON DIOXIDE lactose monohydrate HYDROXYPROPYL CELLULOSE, LOW SUBSTITUTED HYPROMELLOSE 2910 (6 MPA.S) titanium dioxide FERRIC OXIDE YELLOW Product Characteristics Color Size Imprint Code Shape YELLOW (Yellow) 9 mm 0;8;A CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:13107-031-30 30 in 1 BOTTLE 2 NDC:13107-031-34 30 in 1 BOTTLE 3 NDC:13107-031-60 60 in 1 BOTTLE 4 NDC:13107-031-90 90 in 1 BOTTLE 5 NDC:13107-031-01 100 in 1 BOTTLE 6 NDC:13107-031-05 500 in 1 BOTTLE 7 NDC:13107-031-32 30 in 1 BLISTER PACK Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA076921 2009-08-17

Mirtazapine Mirtazapine TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:13107-003 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength MIRTAZAPINE Mirtazapine 30 mg Inactive Ingredients Ingredient Name Strength STARCH, CORN hydroxypropyl cellulose MAGNESIUM STEARATE SILICON DIOXIDE lactose monohydrate HYDROXYPROPYL CELLULOSE, LOW SUBSTITUTED HYPROMELLOSE 2910 (6 MPA.S) titanium dioxide FERRIC OXIDE YELLOW ferric oxide red FERROSOFERRIC OXIDE Product Characteristics Color Size Imprint Code Shape BROWN (Reddish Brown) 14 mm 0;9;A CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:13107-003-30 30 in 1 BOTTLE 2 NDC:13107-003-34 30 in 1 BOTTLE 3 NDC:13107-003-60 60 in 1 BOTTLE 4 NDC:13107-003-90 90 in 1 BOTTLE 5 NDC:13107-003-01 100 in 1 BOTTLE 6 NDC:13107-003-05 500 in 1 BOTTLE 7 NDC:13107-003-32 30 in 1 BLISTER PACK Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA076921 2009-08-17

Mirtazapine Mirtazapine TABLET, FILM COATED Product Information Product Type Human prescription drug label Item Code (Source) NDC:13107-032 Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength MIRTAZAPINE Mirtazapine 45 mg Inactive Ingredients Ingredient Name Strength STARCH, CORN hydroxypropyl cellulose MAGNESIUM STEARATE SILICON DIOXIDE lactose monohydrate HYDROXYPROPYL CELLULOSE, LOW SUBSTITUTED HYPROMELLOSE 2910 (6 MPA.S) titanium dioxide Product Characteristics Color Size Imprint Code Shape WHITE 14 mm 10;A CAPSULE Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:13107-032-34 30 in 1 BOTTLE 2 NDC:13107-032-60 60 in 1 BOTTLE 3 NDC:13107-032-90 90 in 1 BOTTLE 4 NDC:13107-032-01 100 in 1 BOTTLE 5 NDC:13107-032-05 500 in 1 BOTTLE 6 NDC:13107-032-32 30 in 1 BLISTER PACK Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA076921 2009-08-17